Effects of progesterone (P) and antiprogestin RU486 on LH and FSH release by incubated pituitaries from rats treated with the SERM LY117018-HCl and/or recombinant human FSH

Abstract

The aim of the present study was to investigate the role of the estrogen (ES) background on the effects of P or its antagonist RU486 on basal and LHRH-stimulated LH and FSH secretion. To do this, pituitaries collected from: intact rats in proestrus; rats injected with the ES antagonist LY11701 8-HCl; rats injected with recombinant-human FSH (r-hFSH) to stimulate ovarian hormonogenesis; and rats injected with both LY11701 8-HCl and r-hFSH were incubated with or without LHRH (10 nM) in the presence of P (100 nM) or RU486 (10 nM). RU486 decreased basal and LHRH-stimulated release of LH and FSH and LHRH self-priming in pituitaries from control rats, while P increased both pituitary responsiveness and LHRH self-priming. These effects were absent in pituitaries from rats treated either with the ES antagonist or r-hFSH, which, in the absence of P or RU486 in the incubation medium, reduced gonadotropin release. Because r-hFSH did not increase E2 serum concentration significantly, the putative FSH-dependent ovarian non-steroidal gonadotropin surge inhibiting factor (GnSIF) might be the hormonal cause of the reduced secretion of LH and FSH. Combined treatment with LY117018-HCl and r-hFSH had additive inhibitory effects on gonadotropin release. These results indicate that ES-inducible P receptor (PR) in the pituitary can be activated in a ligand-independent manner by intracellular messengers giving rise to enhanced basal and LHRH-stimulated gonadotropin secretion. The results also suggested that the r-hFSH-stimulated ovarian bioactive entity GnSIF and RU486 may share a similar mechanism of action involving pituitary PR.

Expression of estrogen receptors in the hypothalamo-pituitary-ovarian axis in middle-aged rats after re-instatement of estrus cyclicity

“…At the level of the pituitary gland, progesterone has been shown to regulate the magnitude and possibly the duration of the preovulatory gonadotropin surge (Banks and Freeman 1978; Krey and Kamel 1990; Turgeon and Waring 1990). In agreement with these results, Bellido et al (2002) reported that LH and FSH secretion were reduced by application of the antiprogestin RU486 to isolated pituitaries. As RU486 reduces galanin (Sanchez-Criado et al 2001) and activin (Szabo et al 1998) stimulating effects on LH and FSH secretion, progesterone treatment appears to exert direct effects on the pituitary.…”

Gonadotropin surge‐inhibiting/attenuating factors: A review of current evidence, potential applications, and future directions for research

“…While many reports have been on women undergoing ovarian stimulation, GnSIF/AF activity has also been found in follicular fluid from naturally cycling women (Fowler et al, ). Several reports indicated that one of GnSIF/AF's major actions is to maintain the pituitary in a state of low‐sensitivity to GnRH during the early‐ and mid‐follicular phase, and that this effect is augmented by estrogen and progesterone (Byrne et al, ; Byrne et al, ; Tijssen et al, ; de Koning et al, ; Bellido et al, ; Gordon et al, ). One group described FSH as having two effects on LH secretion: stimulating production of GnSIF/AF and directly affecting the pituitary (Hull et al, ).…”